Gut microbiome-mediated modulation of hepatic cytochrome P450 and P-glycoprotein: impact of butyrate and fructo-oligosaccharide-inulin

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dc.contributor.author Walsh, Jacinta
dc.contributor.author Gheorghe, Cassandra E.
dc.contributor.author Lyte, Joshua M.
dc.contributor.author van de Wouw, Marcel
dc.contributor.author Boehme, Marcus
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Cryan, John F.
dc.contributor.author Griffin, Brendan T.
dc.contributor.author Clarke, Gerard
dc.contributor.author Hyland, Niall P.
dc.date.accessioned 2020-04-28T14:21:48Z
dc.date.available 2020-04-28T14:21:48Z
dc.date.issued 2020-04-26
dc.identifier.citation Walsh, J., Gheorghe, C.E., Lyte, J.M., van de Wouw, M., Boehme, M., Dinan, T.G., Cryan, J.F., Griffin, B.T., Clarke, G. and Hyland, N.P. (2020) 'Gut microbiome‐mediated modulation of hepatic cytochrome P450 and P‐glycoprotein: impact of butyrate and fructo‐oligosaccharide‐inulin', Journal of Pharmacy and Pharmacology, doi: 10.1111/jphp.13276 en
dc.identifier.startpage 1 en
dc.identifier.endpage 10 en
dc.identifier.issn 2042-7158
dc.identifier.uri http://hdl.handle.net/10468/9885
dc.identifier.doi 10.1111/jphp.13276 en
dc.description.abstract Objectives: Our objective was to demonstrate microbial regulation of hepatic genes implicated in drug metabolism and transport using germ‐free (GF) mice and to explore the impact of a microbial metabolite, butyrate, and a prebiotic dietary intervention on hepatic gene expression in mice. Methods: Using reverse‐transcriptase PCR, we investigated cytochrome P450 (CYP) and multidrug‐resistance protein 1 (MDR1) expression in conventional, GF and colonised GF mice. To investigate the effects of butyrate, sodium butyrate (3 g/l) was administered for 21 days to conventional or GF mice. In the prebiotic study, young adult and middle‐aged mice received diet enriched with 10% fructo‐oligosaccharide (FOS)‐inulin for 14 weeks. Key findings: Colonisation of GF animals normalised expression of Cyp3a11 and Mdr1b to conventional levels. Butyrate upregulated Cyp2b10 in conventional mice (P < 0.05) but overall did not induce widespread changes in hepatic genes. FOS‐inulin increased Cyp3a13 expression and had the opposite effect on Mdr1a expression in young adult mice (P < 0.05). Age, on the other hand, influenced the prebiotic effect on Cyp2a4 expression (P < 0.01). Conclusion: The expression of hepatic genes implicated in drug metabolism and transport displays sensitivity to the microbiome, microbiome‐derived metabolites and a microbial‐targeted intervention. Our study may provide the impetus to explore microbiota‐targeted interventions in normalising host metabolic activity and reducing inter‐individual variability in drug pharmacokinetics. en
dc.description.sponsorship Nature Research-Yakult (The Global Grants for Gut Health; Ref No. 626891); Joint Programming Initiative-a healthy diet for a healthy life ((JPI-HDHL) award, ‘A Menu for Brain Responses Opposing Stress-Induced Alternations in Cognition’ (AMBROSIAC; 15/JPHDHL/3270)) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Wiley en
dc.rights © 2020 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology. This is the peer reviewed version of the following article: (2020), Gut microbiome‐mediated modulation of hepatic cytochrome P450 and P‐glycoprotein: impact of butyrate and fructo‐oligosaccharide‐inulin. J Pharm Pharmacol., which has been published in final form at https://doi.org/10.1111/jphp.13276 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. en
dc.subject Cytochrome en
dc.subject Hepatic en
dc.subject Metabolism en
dc.subject Microbiome en
dc.subject Transporter en
dc.title Gut microbiome-mediated modulation of hepatic cytochrome P450 and P-glycoprotein: impact of butyrate and fructo-oligosaccharide-inulin en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Niall Hyland, Physiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: n.hyland@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2021-04-26
dc.date.updated 2020-04-28T13:08:48Z
dc.description.version Accepted Version en
dc.internal.rssid 512189042
dc.internal.pmid 32337713
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Yakult Bio-Science Foundation en
dc.contributor.funder Joint Programming Initiative A healthy diet for a healthy life en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal of Pharmacy and Pharmacology en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress n.hyland@ucc.ie en
dc.internal.IRISemailaddress jacinta.walsh@ucc.ie en
dc.internal.IRISemailaddress brendan.griffin@ucc.ie en
dc.internal.IRISemailaddress marcus.boehme@ucc.ie en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.internal.IRISemailaddress t.dinan@ucc.ie en
dc.internal.IRISemailaddress g.clarke@ucc.ie en
dc.internal.bibliocheck In press. Add volume, pages, update citation. en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/ en


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